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Assays & screens

Mass spectrometry profiling of histone modifications

Mass spectrometry profiling of histone modifications could be used to discover new cancer targets that modify chromatin. Mass spectrometry analysis of 42 combinations of histone H3 modifications across 115 cancer cell lines enabled partitioning of cell subsets by chromatin state. Further DNA sequence analysis and gene expression profiling led to the identification of a subgroup of acute lymphoblastic leukemia (ALL) cells carrying E1099K activating mutations in the nuclear SET domain-containing protein 2 (NSD2; MMSET; WHSC1) methyltransferase. In cell culture and mouse xenograft models carrying this mutation, small hairpin RNA knockdown of NSD2 decreased growth compared with no knockdown. Next steps include expanding the method for use in patient stratification and selection (see NSD2 momentum, page1).

SciBX 6(39); doi:10.1038/scibx.2013.1105
Published online Oct. 10, 2013

Patent application filed covering discovery of oncogenic NSD2-E1099K mutations and molecular chromatin signatures that predict response to NSD2 inhibition; licensing status undisclosed

Jaffe, J.D. et al. Nat. Genet.; published online Sept. 29, 2013;
Contact: Frank Stegmeier, Novartis Institutes for BioMedical Research, Cambridge, Mass.
Contact: Levi A. Garraway, Broad Institute of MIT and Harvard, Cambridge, Mass.